{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T06:33:08Z","timestamp":1791181988452,"version":"4.1.0"},"reference-count":56,"publisher":"American Society of Hematology","issue":"3","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mutations in the proto-oncogene c-kit cause constitutive kinase activity of its product, KIT protein, and are associated with human mastocytosis and gastrointestinal stromal tumors (GISTs). Although currently available tyrosine kinase inhibitors are effective in the treatment of GISTs, there has been limited success in the treatment of mastocytosis. 17-Allylamino-17-demethoxygeldanamycin (17-AAG), a benzoquinoid ansamycin antibiotic, which binds to heat shock protein 90 (hsp90) causes destabilization of various hsp90-dependent kinases important in oncogenesis. Treatment with 17-AAG of the mast cell line HMC-1.2, harboring the Asp816Val and Val560Gly KIT mutations, and the cell line HMC-1.1, harboring a single Val560Gly mutation, causes both the level and activity of KIT and downstream signaling molecules AKT and STAT3 to be down-regulated following drug exposure. These data were validated using Cos-7 cells transfected with wild-type and mutated KIT. 17-AAG promotes cell death of both HMC mast cell lines. In addition, neoplastic mast cells isolated from patients with mastocytosis, incubated with 17-AAG ex vivo, are selectively sensitive to the drug compared to the mononuclear fraction. These data provide compelling evidence that 17-AAG may be effective in the treatment of c-kit-related diseases including mastocytosis, GISTs, mast cell leukemia, subtypes of acute myelogenous leukemia, and testicular cancer. (Blood. 2004;103:1078-1084)<\/jats:p>","DOI":"10.1182\/blood-2003-07-2477","type":"journal-article","created":{"date-parts":[[2003,10,14]],"date-time":"2003-10-14T00:18:45Z","timestamp":1066090725000},"page":"1078-1084","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":121,"title":["17-Allylamino-17-demethoxygeldanamycin (17-AAG) is effective in down-regulating mutated, constitutively activated KIT protein in human mast cells"],"prefix":"10.1182","volume":"103","author":[{"given":"Gerard","family":"Fumo","sequence":"first","affiliation":[{"name":"From the Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Akin","sequence":"additional","affiliation":[{"name":"From the Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dean D.","family":"Metcalfe","sequence":"additional","affiliation":[{"name":"From the Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Len","family":"Neckers","sequence":"additional","affiliation":[{"name":"From the Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Rockville, MD; and Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021300060473100_REF1","doi-asserted-by":"crossref","unstructured":"Yarden Y, Kuang WJ, Yang-Feng T, et al. 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